The Global Burden of Diabetic Kidney Disease: Time Trends and Gender Gaps.

PURPOSE OF REVIEW: Diabetes mellitus prevalence is increasing throughout the world as a consequence of growing rates of obesity, metabolic syndrome, and westernization of lifestyle. It is currently unknown to what extent these trends affect the global burden of diabetic kidney disease (DKD). This review seeks to describe the global burden of DKD and how it has changed throughout time using recently released results of the Global Burden of Disease 2017 Study. RECENT FINDINGS: DKD prevalence has remained fairly stable at the global level and among many world regions since 1990. At the global level, the proportion of DKD deaths relative to other types of CKD is increasing. Certain world regions still have very high rates of DKD, whereas other world regions have decreasing prevalence and mortality. Screening will likely play an important role in mitigating the growing burden within high-risk regions.

Global Cardiovascular and Renal Outcomes of Reduced GFR.

The burden of premature death and health loss from ESRD is well described. Less is known regarding the burden of cardiovascular disease attributable to reduced GFR. We estimated the prevalence of reduced GFR categories 3, 4, and 5 (not on RRT) for 188 countries at six time points from 1990 to 2013. Relative risks of cardiovascular outcomes by three categories of reduced GFR were calculated by pooled random effects meta-analysis. Results are presented as deaths for outcomes of cardiovascular disease and ESRD and as disability-adjusted life years for outcomes of cardiovascular disease, GFR categories 3, 4, and 5, and ESRD. In 2013, reduced GFR was associated with 4% of deaths worldwide, or 2.2 million deaths (95% uncertainty interval [95% UI], 2.0 to 2.4 million). More than half of these attributable deaths were cardiovascular deaths (1.2 million; 95% UI, 1.1 to 1.4 million), whereas 0.96 million (95% UI, 0.81 to 1.0 million) were ESRD-related deaths. Compared with metabolic risk factors, reduced GFR ranked below high systolic BP, high body mass index, and high fasting plasma glucose, and similarly with high total cholesterol as a risk factor for disability-adjusted life years in both developed and developing world regions. In conclusion, by 2013, cardiovascular deaths attributed to reduced GFR outnumbered ESRD deaths throughout the world. Studies are needed to evaluate the benefit of early detection of CKD and treatment to decrease these deaths.

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks. FUNDING: Bill & Melinda Gates Foundation.

Clinical nephrology research in low-resource settings: opportunities, priorities, and challenges for young investigators.

The increased recognition of the growing, worldwide burden of kidney disease has led to calls for prioritizing nephrology research in a global context. However, many challenges exist for young investigators interested in studying kidney disease in low-resource global settings. A lack of clear research priorities, limited funding options, poor infrastructure, difficulty forming partnerships, and unestablished paths for career advancement are a few examples. To discuss these issues, we held a moderated panel discussion in March 2015 as part of the 10th Conference on Kidney Disease in Disadvantaged Populations in Cape Town, South Africa. A group of senior investigators discussed research priorities for studying kidney disease in a global context, collaborations for clinical research, and strategies for dealing with the unique challenges faced by young investigators working in this field.

Maintenance Dialysis throughout the World in Years 1990 and 2010.

Rapidly rising global rates of chronic diseases portend a consequent rise in ESRD. Despite this, kidney disease is not included in the list of noncommunicable diseases (NCDs) targeted by the United Nations for 25% reduction by year 2025. In an effort to accurately report the trajectory and pattern of global growth of maintenance dialysis, we present the change in prevalence and incidence from 1990 to 2010. Data were extracted from the Global Burden of Disease 2010 epidemiologic database. The results are on the basis of an analysis of data from worldwide national and regional renal disease registries and detailed systematic literature review for years 1980-2010. Incidence and prevalence estimates of provision of maintenance dialysis from this database were updated using a negative binomial Bayesian meta-regression tool for 187 countries. Results indicate substantial growth in utilization of maintenance dialysis in almost all world regions. Changes in population structure, changes in aging, and the worldwide increase in diabetes mellitus and hypertension explain a significant portion, but not all, of the increase because increased dialysis provision also accounts for a portion of the rise. These findings argue for the importance of inclusion of kidney disease among NCD targets for reducing premature death throughout the world.

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Correction: Evaluation of a multi-faceted diabetes care program including community-based peer educators in Takeo province, Cambodia, 2007-2013.

[This corrects the article DOI: 10.1371/journal.pone.0181582.].

Chronic Kidney Disease, Gender, and Access to Care: A Global Perspective.

Little is known regarding the ways in which chronic kidney disease (CKD) prevalence and progression differ between the sexes. Still less is known regarding how social disparities between men and women may affect access to care for CKD. In this review, we briefly describe biological sex differences, noting how these differences currently do not influence CKD management recommendations. We then describe what is known within the published literature regarding differences in CKD epidemiology between sexes; namely prevalence, progression, and access to treatment throughout the major world regions. We highlight that health care expenditure and social gender disparities ultimately may determine whether women have equitable access to care for CKD and end-stage kidney disease. Among many high- and low-income settings, women more often donate and are less likely to receive kidney transplants when compared with men. Research is needed urgently to elucidate the reasons behind these disparities, as well as to develop CKD treatment strategies tailored to women's unique health care needs.

Evaluation of a multi-faceted diabetes care program including community-based peer educators in Takeo province, Cambodia, 2007-2013.

INTRODUCTION: Early detection and treatment for diabetes are essential for reducing disability and death from the disease. Finding effective screening and treatment for individuals living with diabetes in resource-limited countries is a challenge. MoPoTsyo, a Cambodian non-governmental organization, addressed this gap by utilizing a multi-pronged approach with community-based peer educators, access to laboratory procedures, local outpatient medical consultation, and a revolving drug fund. This study evaluated outcomes of MoPoTsyo's diabetes program in Takeo Province by assessing glycemic and blood pressure outcomes for individuals diagnosed with diabetes over a 24-month follow-up period between 2007-2013. METHODS: This is a retrospective cohort analysis of records without a comparison group. We calculated the mean fasting blood glucose (FBG) and blood pressure (BP) at regular intervals of follow-up. The proportion of patients reaching recommended treatment targets for FBG and BP was assessed. RESULTS: Of the 3411 patients enrolled in the program, 2230 were included in the study. The cohort was predominantly female (68.9%) with a median age of 54 years. Median follow-up time in the program was 16 months (4.9-38.4 months). Mean FBG decreased 63.9 mg/dl in mean FBG (95% CI 58.5 to 69.3) at one year of follow-up (p<0.001). After one year, 45% (321/708) of patients achieved goal FBG < 126. Of the 41.6% (927/2230) with elevated BP at enrollment, systolic and diastolic BP levels significantly decreased (p<0.001) by 16.9 mmHg (95% CI 1.2 to 22.9) and 10 mm Hg (95% CI 0.7 to 12.9) respectively between enrollment and one year of follow-up. At one year of follow-up, 51.1%% (183/355) of these patients reached the BP goal < 140/90. CONCLUSION: The improved outcome indicators of diabetes care for MoPoTsyo's Takeo program evaluation showed promise. The program demonstrated a reasonable and practical approach to delivering effective diabetes care in a rural area and may serve as a model for other low-income communities. Future prospective evaluations with more complete data are necessary for longer-term outcomes.

Action plan for determining and monitoring the prevalence of chronic kidney disease.

Chronic kidney disease (CKD) continues to remain high globally, up to 13.4% by one estimate. Although the number, geographic distribution, size, and quality of the studies examining CKD prevalence and incidence have increased over the past decade, the global capacity for CKD surveillance is still far less developed than that for hypertension, diabetes, and cardiovascular disease. Estimating CKD prevalence is constrained by inadequate standardization of serum creatinine and urine albumin assays, heterogeneity in study designs, lack of national registries in many countries, incomplete adoption of disease classification guidelines, and inconsistent use of evidence-based equations for estimating glomerular filtration rate. Goal 1: Improve monitoring of CKD prevalence. To achieve this, disseminate the rationale for CKD prevalence monitoring, achieve uniform measurement of CKD markers, promote inclusion of CKD measurements in all large chronic disease cohorts and health surveys, harness administrative claims data for CKD surveillance, and incorporate the new CKD classification system in the International Classification of Diseases. Goal 2: Improve CKD monitoring of populations underrepresented in studies to date. To achieve this, establish registries of chronic dialysis and transplantation in all countries; establish registries for special CKD groups, such as children, patients with rare diseases, and patients with special etiologies of CKD. Goal 3: Improve identification of individuals with CKD. To achieve this, implement the Kidney Disease: Improving Global Outcomes guidelines for screening and testing, carry out randomized studies on screening strategies, ensure that estimated glomerular filtration rate is reported with all reports of serum creatinine, and leverage new software for identification and follow-up of CKD cases.

Strategies to improve monitoring disease progression, assessing cardiovascular risk, and defining prognostic biomarkers in chronic kidney disease.

Chronic kidney disease (CKD) is a major global public health problem with significant gaps in research, care, and policy. In order to mitigate the risks and adverse effects of CKD, the International Society of Nephrology has created a cohesive set of activities to improve the global outcomes of people living with CKD. Improving monitoring of renal disease progression can be done by screening and monitoring albuminuria and estimated glomerular filtration rate in primary care. Consensus on how many times and how often albuminuria and estimated glomerular filtration rate are measured should be defined. Meaningful changes in both renal biomarkers should be determined in order to ascertain what is clinically relevant. Increasing social awareness of CKD and partnering with the technological community may be ways to engage patients. Furthermore, improving the prediction of cardiovascular events in patients with CKD can be achieved by including the renal risk markers albuminuria and estimated glomerular filtration rate in cardiovascular risk algorithms and by encouraging uptake of assessing cardiovascular risk by general practitioners and nephrologists. Finally, examining ways to further validate and implement novel biomarkers for CKD will help mitigate the global problem of CKD. The more frequent use of renal biopsy will facilitate further knowledge into the underlying etiologies of CKD and help put new biomarkers into biological context. Real-world assessments of these biomarkers in existing cohorts is important, as well as obtaining regulatory approval to use these biomarkers in clinical practice. Collaborations among academia, physician and patient groups, industry, payer organizations, and regulatory authorities will help improve the global outcomes of people living with CKD.

Allograft inflammatory factor-1 expression correlates with cardiac rejection and development of cardiac allograft vasculopathy.

BACKGROUND: Standard morphological features of endomyocardial biopsy specimens do not necessarily correlate with the efficacy of immunotherapy or development of cardiac allograft vasculopathy (CAV). We hypothesized that expression of allograft inflammatory factor-1 (AIF-1), a cytokine-inducible, calcium-binding protein associated with vascular smooth muscle cell proliferation, would be associated with allograft rejection and development of CAV. METHODS AND RESULTS: A total of 157 endomyocardial biopsy specimens from 26 patients with heart transplants were examined for expression of AIF-1 mRNA by semiquantitative reverse transcription-polymerase chain reaction. A significant relation was found between the International Society for Heart and Lung Transplantation rejection grade and expression of AIF-1 (P<0.001). The calculated odds ratio indicates that a biopsy has 2.5 times the chance of AIF-1 expression per grade of rejection. The relative concentrations of AIF-1 and GAPDH mRNA were calculated and the resulting ratios indicated that the amount of AIF-1 mRNA expression is relative to the rejection grade (P<0.02). In grade 1 biopsy specimens, AIF-1 was localized to infiltrating immune cells. In grade 3 biopsy specimens, AIF-1 was observed in immune cells and myocytes. AIF-1 is expressed in vascular and immune cells in coronary arteries with CAV, and persistent expression of AIF-1 in the allograft correlates with development of CAV (P<0.002). CONCLUSIONS: Expression of AIF-1 in cardiac allografts correlates with rejection, and the amount of AIF-1 expressed correlates with the severity of rejection. AIF-1 is expressed in coronary arteries with CAV, and persistent expression of AIF-1 in the cardiac allograft is associated with development of CAV.

An estimation of the prevalence and progression of chronic kidney disease in a rural diabetic cambodian population.

BACKGROUND: To date, there are no known estimates of the prevalence of chronic kidney disease within Cambodia, the vast majority of whose citizens live in rural areas with limited access to renal replacement therapy. METHODS: Observational analysis of patients from the Takeo province in Cambodia who presented to MoPoTsyo, a non-governmental organization, for screening and management of diabetes mellitus between 2010 and 2012 (n = 402; 75% females). Estimated glomerular filtration rate (eGFR) was calculated using the CKD-Epi equation. RESULTS: On average, women were younger, with a higher percentage of hypercholesterolemia but also high-density lipoprotein level. Men had a higher serum creatinine level (1.31 mg/dl) than that of women (1.13 mg/dl) at 95% CI. More than half of all screened patients had a reduced eGFR; 60% (95% CI 55%, 65%) had an eGFR<60 ml/min/1.73 m(2); 54% (49%, 59%) had an eGFR 30-60 ml/min/1.73 m(2), and 5.7% (3.4%, 8.0%) with eGFR 15-30 ml/min/1.73 m(2). Women had a greater prevalence of stage 3 CKD (57% women vs. 47% men) and stage 4 CKD (7.0% vs. 2.0%). The adjusted odds ratio for females compared to males having an eGFR <60 ml/min/1.73 m(2) was 3.19 (95% CI 1.78, 5.43; p value<0.001). Thirty-two percent of patients lost ≥ 5 ml/min/1.73 m2 eGFR during median follow-up time of 433 days (IQR 462 days) days. CONCLUSIONS: Over one-half of Cambodians with diabetes mellitus had reduced eGFR, implying a point-prevalence of chronic kidney disease of 1.2% in among adult Cambodians within the country. This high burden of kidney disease in a society that lacks universal access to renal replacement therapy underscores the importance of early diagnosis - a largely unmet need in Cambodia.

Geographic variation in black-white differences in end-of-life care for patients with ESRD.

BACKGROUND AND OBJECTIVES: Patterns of end-of-life care among patients with ESRD differ by race. Whether the magnitude of racial differences in end-of-life care varies across regions is not known. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This observational cohort study used data from the US Renal Data System and regional health care spending patterns from the Dartmouth Atlas of Healthcare. The cohort included 101,331 black and white patients 18 years and older who initiated chronic dialysis or received a kidney transplant between June 1, 2005, and September 31, 2008, and died before October 1, 2009. Black-white differences in the odds of in-hospital death, dialysis discontinuation, and hospice referral by quintile of end-of-life expenditure index (EOL-EI) were examined. RESULTS: In adjusted analyses, the odds ratios for dialysis discontinuation for black versus white patients ranged from 0.47 (95% confidence interval=0.43 to 0.51) in the highest quintile of EOL-EI to 0.63 (95% confidence interval=0.54 to 0.74) in the lowest quintile (P for interaction<0.001). Hospice referral ranged from 0.55 (95% confidence interval=0.50 to 0.60) in the highest quintile of EOL-EI to 0.82 (95% confidence interval=0.69 to 0.96) in the lowest quintile (P for interaction<0.001). The association of race with in-hospital death also differed in magnitude across quintiles of EOL-EI, ranging from 1.21 (95% confidence interval=1.08 to 1.35) in the highest quintile of EOL-EI to 1.47 (95% confidence interval=1.27 to 1.71) in the second quintile (P for interaction<0.001). CONCLUSIONS: There are pronounced black-white differences in patterns of hospice referral and dialysis discontinuation among patients with ESRD that vary substantially across regions of the United States.

Renal replacement therapy in congestive heart failure requiring left ventricular assist device augmentation.

"Cardiorenal syndrome" is a term used to describe a dys-regulation of the heart affecting the kidneys, or vice versa, in an acute or chronic manner (1,2). Renal impairment can range from reversible ischemic damage to renal failure requiring short- or long-term renal replacement therapy (2). Patients who require mechanical circulatory support, such as a left ventricular assist device (LVAD), as definitive treatment for congestive heart failure or as a bridge to cardiac transplantation pose a unique challenge with respect to receiving dialysis, because they experience higher rates of morbidity and mortality from infection in the post-LVAD period (3-7). Acute dialysis access can pose an increased infection risk. In this article, we present a patient who required renal replacement therapy and a LVAD for management of acute-on-chronic cardiorenal syndrome while awaiting heart transplantation. A literature review to determine whether peritoneal dialysis or hemodialysis is superior for patients with profound hemodynamic dysfunction and the need to minimize risk of infection did not offer clear guidance about which modality is superior in patients with advanced congestive heart failure. However, there is clear evidence of the superiority of peritoneal dialysis in reducing the risk of systemic infection secondary to acute dialysis access. Given the high risk of LVAD infection, we therefore conclude that, to decrease mortality secondary to systemic infection, peritoneal dialysis should strongly be considered in patients who require renal replacement therapy before or after LVAD placement.

Improving blood pressure control among adults with CKD and diabetes: provider-focused quality improvement using electronic health records.

Current evidence demonstrates poor provider knowledge and compliance to clinical practice guidelines (CPGs) for CKD screening, blood pressure (BP) goals specific to people with diabetes mellitus (DM) and CKD, and underutilization or incorrect drug selection for antihypertensive therapy. This 12-week provider-focused quality improvement project sought to (1) increase primary care provider (PCP) adherence to CPG in the treatment and control of BP among adults with CKD and DM by using electronic health records (EHRs) and patient-level feedback (scorecards); (2) increase PCP delivery of basic CKD patient education by using EHR-based decision support; and (3) assess whether electronic decision support and scorecards changed provider behavior. The project included 46 PCPs, physicians, and nurse practitioners, in a statewide federally qualified health center that operates 12 comprehensive primary care sites in Connecticut. There were 6781 DM visits, among 3137 unique, racially diverse patients. There was a statistically significant increase in CKD screening, diagnosis, and use of angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker. There was a statistically, but not clinically, significant increase in CKD basic education and ancillary service provider use when the provider was aware of the diagnosis or used EHR enhancements. EHR decision support and real-time provider feedback are necessary but not sufficient to improve uptake of CPG and to change PCP behavior.